The ability of low levels of fluoride ions to protect teeth against the development of carious lesions is well known, although the mechanism by which the protective effect is exerted still is only poorly understood. It has been shown that fluoride can affect both the tooth enamel and the metabolism of acidogenic microorganism in plaque. Our interest has been in the latter and we have shown, in the early phase of this investigation, that low levels (1-10 ppm) of fluoride affect various strains of oral streptococci to differing degrees. It was suggested that such behavior of plaque microorganisms might explain the variability of clinical responses to water fluoridation. However, the basis for the variation in response to fluoride among the strains remained unexplained. In recent studies we have established that the properties of the enolases from different streptococci are inhibited in the same manner and to the same degree by fluoride so that the differences in the cellular responses to F minus are not explained by any differences in the target enzyme. The isolated enolases have been shown to bind fluoride and further studies with yeast enolase, as a model, have demonstrated the enhancing effect of H ion, MG 2 ion and inorganic phosphate on the binding mechanism. Current experiments deal with the measurement of intracellular pH in the different strains and the possible effects that these may have in determining the metabolic responses to F minus. It is expected that the information that will be gained from this study will help us to understand the basic biochemical events that give rise to the inhibition of bacterial metabolism by fluoride. This should enable us to determine why there are limitations to the clinical effectiveness of fluoride, and may lead to more effective approaches for the delivery of fluoride.